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ACR name badgeWhat a first day at the American College of Rheumatology (ACR) Conference! I heard that there are over 15,000 people here and they are from all over the world. I spent the morning volunteering at the Rheumatoid Patient Foundation (RPF) booth and then attended sessions in the afternoon. I met the wonderful people from the Arthritis National Research Foundation and Arthritis Introspective. The exhibit hall was overwhelming!

If you want to receive regular updates via Twitter, I’m @livingwra.

Here’s a list of topics I plan to write about over the next few weeks as I have time to process information.

  1. Pharma companies spend lots of money at conferences (and give free lattes).
  2. Personalized medicine based on genomics and autoantibody profiles may be in the future.
  3. Biomarkers for various various signaling pathways may help select targeted kinase inhibitors.
  4. Autoimmune antibody markers other than Rheumatoid Factor (RF) and Anti-CCP are being investigated in order to better predict RA.
  5. People with positive RF and Anti-CCP tests tend to have higher levels of inflammatory cytokines.
  6. The lung is being investigated as a possible site of RA initiation.
  7. Systemic inflammation in RA contributes to depression.

More updates tomorrow and details about our paper presentation on Tuesday to follow.

ACR exhibit hall

 

 

 

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I’ve been absent from this blog for almost 1 ½ years, I decided to jump back and start writing again. And much has transpired since the last post. After stringing it out as long as possible, I had my third ankle surgery in late November 2011. The orthopedic surgeon cleaned up bone erosion on the top side of the heel bone, removed a bone spur poking into my Achilles tendon, removed a bursa sac, and repaired mores tears in the Achilles tendon. Tissues samples were sent to pathology and the lab results noted bone erosion and inflammation caused by rheumatoid arthritis.

Stopping Humira injections in early November 2011 was necessitated by the pending ankle surgery but also by the fact that it just wasn’t helping that much anymore. In addition, a 3 cm swollen lymph node in my armpit needed to be checked out. Short story – saw a great oncologist and after many blood tests, an ultrasound, and a CT scan with iodine contrast, everything came back negative with no lymphoma! One interesting blood test result was that I had a positive Rheumatoid Factor test for the first time. I was finally seropositive and felt like I was no longer the seronegative stepchild of RA. Although I know that upwards of 30% of folk don’t have positive RA blood tests.

I was started on Orcenia infusions in January 2012. I was done with TNF blockers after using Enbrel, Cimzia, and Humira. After insurance approval, I had three loading doses every two weeks before moving to a regular schedule of once a month. Having a nurse administered infusion at a clinic was a new experience compared to self-injections of Enbrel and Humira. It was a rough few months but I began to get back some energy and have less joint pain and stiffness.

By this point, I decided to pursue a new rheumatologist. I had been with my original rheumatologist from the beginning and he made the initial diagnosis. But over time I began to realize that it was time for a change. I sought out a new rheumy by asking around, checking out published lists of top doctors in the region, and looking at patient reviews online. A choice was made and an appointment with a new rheumy scheduled. As an added advantage, her clinic just relocated to a brand new, clean, and cheery building. I had all medical records sent to her.

The first appointment was a pleasant experience from the beginning with smiling staff, caring nurses, and the fact that I didn’t have to wait. The first thing the doctor told me was that she spent considerable time reading all of my medical records. That was a refreshing to know – she already had an idea about my case before I arrived. She then asked me to tell my story in my own words. Given my history, my new rheumy suspects that I may have a combination of RA and ankylosing spondylitis – an autoimmune condition which commonly affects ankles, hips, and backs. She joked that I would be a good subject for genetic testing! We discussed how Orencia was working and she felt like I would benefit from the addition of a disease modifying drug (DMARD). Since methotrexate and I didn’t have a good relationship a few years ago, she wanted to try leflunomide (Arava). In fact, she suspects that one reason that TNF blockers stopped working was that I wasn’t on combination therapy resulting in the building up of antibodies to Enbrel and Humira. I appreciated her optimism about being able to help and compassion about my experiences.

New adventures lie ahead with a new doctor, new medicines, and new possible side effects. But hope springs eternal just like the sun finally coming out in Seattle.

Photo taken by my daughter on a sunny day in Puget Sound.

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Humira - sunday week 12

Image by pollyalida via Flickr

Things are pretty hectic these days and that typically brings an increase in fatigue and joint symptoms. It doesn’t help that my Humira injection is due tomorrow but I’m itching to take it today with the notion that it may help me feel better. Of course, today I read of a study demonstrating that stress increases the release of inflammatory proteins like TNF alpha.[i] But I was more intrigued by the Arthritis Foundation article about how long it takes for rheumatic diseases to be diagnosed.[ii] Average time to diagnosis varies (see table below) but it is clear that folks with these diseases suffer for a long time before getting proper treatments. The article states, “Many rheumatic diseases have symptoms that overlap, and blood tests are rarely conclusive.”

Rheumatoid arthritis 6 to 9 months
Juvenile arthritis             5 months
Fibromyalgia                    2 to 5 years
Sjögren’s syndrome         3 to 7 years
Ankylosing spondylitis    6 to 9 years

Such was the case with me. After being referred by my general practitioner (an internist), my rheumatologist first suspected ankylosing spondylitis since my primary symptoms at the time were uveitis (inflammation of the iris) and achilles tendon problems. But my blood test for HLA-B27, the common genetic marker for this disease, was negative. About the same time, other tell-tale symptoms of RA began appearing…middle finger joints, wrists, elbows, knees – all occurring symmetrically on both sides. Bone erosion was noted via x-rays. Morning stiffness (what’s that? I’m stiff all day long!) and overwhelming fatigue (the truck running over you type) wrapped it up for the rheumy and he diagnosed me with RA.

This diagnosis was made in spite of negative RA factor blood tests. My RA factor tests have always been “borderline”…it’s not a black and white test. Another antibody test, anti-cyclic citrullinated peptide (anti-CCP) is another one used to determine RA. So far, I’ve been negative on that one as well. Therefore, I have what is called “seronegative RA.” I met the criteria using the now outdated diagnostic criteria.[iii] The diagnosis criteria were recently updated[iv] and according this new system, I still meet the diagnostic critieria without having positive blood tests. My rheumy regularly mentions that seronegative RA patients tend to fare better with symptoms over the long run and this is borne out by research.[v] Some seronegative RA patients “convert” over time…they end up with positive tests. Interestingly, a large proportion of folks diagnosed with RA are seronegative…up to 30% in some studies.[vi]

Being seronegative makes me feel somewhat like the stepchild to those who are seropositive. Maybe I’m not “official enough”. But then I have to step back and remember that my symptoms are real, I have permanent joint damage, and I’m forking out upwards of $20,000 a year for biological treatments (well ok, my insurance covers most of it). Perhaps I will seroconvert someday. But in the meantime I’ll hang onto the research that says that us seronegative RA types have a better long term prognosis.


[i] http://www.arthritistoday.org/news/social-rejection-stress-inflammation080.php

[ii] http://www.arthritistoday.org/daily-living/relationships/you-and-your-doctor/rheumatic-diseases-misdiagnosed.php

[iii] http://www.hopkins-arthritis.org/physician-corner/education/acr/acr.html

[iv] http://www.rheumatology.org/practice/clinical/classification/ra/2010_revised_criteria_classification_ra.pdf

[v] http://www.ncbi.nlm.nih.gov/pubmed/3855618

[vi] http://onlinelibrary.wiley.com/doi/10.1111/j.0105-2896.2009.00856.x/full

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Biological warfare generally refers to the use of pathogens (infectious agents) such as viruses or bacteria that are delivered to an enemy. The term, as applied to the treatment of RA, really refers to the use of antibodies produced via biological processes. These antibodies are designed to target biological processes of RA.

Wikipedia Commons

The biological basis for RA was outlined in an earlier blog post. In that post, the biochemical picture of RA in simplistic terms was outlined as follows:

  • Something unknown triggers lymphocytes (T-cells, B-cells)
  • Lymphocytes trigger Tumor Necrosis Factor (TNF) and inflammation
  • TNF induces another chemical called RANKL
  • RANKL promotes the production of osteoclasts (special bone cells)
  • Osteoclasts erode bone tissue.

Once these processes began to be understood in the 1980s and 90s, scientists starting developing and testing biological treatments for RA. These treatments are disease modifying (DMARDs) in the sense that they modify or slow the effects of the disease. Compared to other traditional weapons in the fight against RA, biologicals demonstrate more effectiveness in disease modification. They are even more effective when combined with the use of methotrexate. There are currently 18 biological treatments approved by the FDA and eight are approved for use in rheumatoid arthritis. [i] Being that these treatments consist of complex and fragile proteins, they must be injected into the body.

Due to the complex procedures needed to develop and manufacture biological treatments, they are very expensive, typically costing $15,000 – $30,000 per year. Pharmaceutical companies currently have a 14 year lock on the copyright on biologicals (it’s 7 years for small chemical drugs). But there may be traction in the Congress and by President Obama to change this so cheaper, generic versions are available. [ii] [iii] The cost of these treatments raises cost/benefit questions (“pharmacoeconomics”-hopefully a future blog topic). Never the less, it has been shown that the effectiveness of biologics reduces the number of work days missed and disability claims. [iv]

Like many chemical RA drugs, biological treatments suppress the immune system in the fight against RA. This leads to higher incidents of lymphomas and serious infections in patients who use them. But most RA patients would agree that the benefits far outweigh potential risks.

Below is a table displaying the currently approved biological treatments for RA. [v] [vi] [vii] [viii]

Common Name Antibody Name Manufacturer Mechanism Date FDA Approved in U.S. for RA Typical Administration
Enbrel Etanercept Amgen &  Wyeth Inhibits TNF 1998 Weekly subcutaneous injection
Remicade Infliximab Centocor Ortho Biotech Inhibits TNF 1999 Infusion every 8 weeks
Kineret Anakinra Amgen Inhibits Interlukin-1 2001 Daily subcutaneous injection
Humira Adalimumab Abbott Inhibits TNF 2002 Twice monthly subcutaneous injection
Rituxan Rituximab Genentech Inhibits B-cells 2006 Two initial infusions then every 24 weeks
Simponi Golimumab Centocor Ortho Biotech Inhibits TNF 2009 Monthly subcutaneous injection
Cimzia Certolizumab pegol UCB Inhibits TNF 2009 Monthly subcutaneous injection
Orencia Abatacept Bristol-Myers Squibb Inhibits T-cells 2009 Monthly infusion

Many of the RA blogosphere community members have experience with these biological treatments. I had an initial five month experience injecting Enbrel every week. Monday morning brought with it the joy of using their autoinjector pens. Within a few weeks I felt like I got my life back. My energy levels soared and my rheumatologist was quite pleased with my progress. But after 3-4 months I could feel myself slipping back into full blown RA symptoms. My rheumatologist suggested that I try a newly approved TNF inhibitor called Cimzia. It is designed to stay in the body longer and only requires monthly injections. I’m heading into my third month and while I can see an improvement, the jury is still out on its long term effectiveness (see previous post). But the past three days have been wonderful and I’m thankful for these treatments (in spite of the fact that I must jab myself). Some even experience remission after being on biological treatments – this is my hope and dream.

I feel fortunate that I have not experienced any infections since being on biological treatments. Colds and swine flu visited several members of my household and I was spared every time. I suspect that having a strong immune system prior to treatment helps. My entire professional career has been working in K-12 schools and universities and I’m guessing that I’ve been exposed to plenty infectious pathogens! Getting regular vaccinations to seasonal and H1N1 flu viruses is important (I got both).

Even though RA may take a back seat to other diseases like cancer and heart disease, plenty of scientists continue to hunt for more successful biological treatments (see earlier post). Of all of the weapons currently used in the war against RA, they represent the most effective to date. But there remain several sticky points to their use…costs and infections. Hopefully these issues will be resolved in the future.

Next post…Natural Treatments for RA


[i] http://www.consumer-health.com/services/biological_drugs.htm

[ii] http://www.news-medical.net/news/20090722/Costly-biologics-drugs-prompt-exclusivity-debate.aspx

[iii] http://www.tri-cityherald.com/1182/story/810461.html

[iv] http://ezinearticles.com/?Are-The-New-Biologic-Drugs-For-Rheumatoid-Arthritis-Worth-The-Cost?&id=559432

[v] http://en.wikipedia.org/wiki/Monoclonal_antibodies

[vi] http://en.wikipedia.org/wiki/List_of_monoclonal_antibodies

[vii] http://www.arthritistoday.org/DrugGuide/drug-chart.php

[viii] http://www.physorg.com/news174077828.html

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A second dose of Cimzia (certolizumab pegol) was injected Wednesday evening. Since Enbrel was no longer working well, my rheumatologist recommended trying a new medication. Cimzia, which was recently approved by the FDA, is designed to stay in the body longer thereby making it more effective. The nurse stated that about 15-20 patients in their office switched to Cimzia after Enbrel and Humira stopped working for them.

Below is a photo showing all the paraphernalia associated with self-administration of the antibody treatment. I do “enjoy” the ergonomically designed syringes!

cimzia

I noticed less fatigue last month after the first injection although joint pain and inflammation continued. The first clear evidence of finger joint bending was noticable. My knee was bothering me after swimming a little (so much for swimming as a good exercise for RA). The fatigue returned over the past few days. Since swine flu made a visit to our house last week (my son had it), I debated whether I should wait to take the second dose. Cimzia lowers the immune system increasing vulnerability to infections. We were still in the incubation period for the flu. But I realized that the toll of RA on my body trumped anything else and I gave myself the second injection. The day after the 2nd injection brought an obvious increase in energy, less “brain fog”, and less joint stiffness and pain.

My rheumy said to give it a good 3-4 months before making any long-term judgements about the efficacy of Cimzia.  Since the pain was still present and finger bending noticeable, my rheumy suggested that I try Mobic (meloxicam) which is a non-steroidal anti-inflammatory (NSAID). I can’t tolerate ibuprofen so we’ll see how this goes. Thus, another weapon is added to the chemical arsenal designed to fight RA in my body.

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One week passed since Cimzia was first injected. I must admit that skepticism prevailed from the beginning since Enbrel stopped working over the past couple of months. This skepticism was grounded in the fact that Cimzia acts on the same system as Enbrel – they both block TNF. But some investigation revealed that the structure and sources of these antibody treatments differ. That alone brought some hope.

In searching out information about Cimzia, I learned more about the systems involved in producing antibody treatments (which actually resulted in a Nobel Prize). Biologicals are typically antibodies – proteins produced as part of the immune system. There are about 20 antibody medicines currently approved by the FDA. Antibody medicines are genetically engineered. It appears that mice play an important role (thank all of your local lab mice). The first developed treatments were mouse proteins and these failed once placed into a human. But genetic developments resulted in the mixing of mouse and human components. Currently approved antibody treatments for RA have a range of mouse and human parts. For example…

  • Remicade (chimeric = 65% human, 35% mouse)
  • Cimzia (humanized = 95% human, 5% mouse)
  • Humira (human = 100% human)

But no matter how much human or mouse protein is in the final product, mice are used somewhere in the development of all of them. That’s why I’m going around teasing my children by making my fingers into mouse whiskers and showing buck teeth.

Yesterday brought a level of energy not felt in over a month. Never the less, hope was suppressed. I think that skepticism is a psychological defense mechanism in order to avoid disappointment. Many with RA travel down this road of dashed hopes as one after another medical treatment is tested and abandoned. But today brought even better news…I woke up quickly, met someone for breakfast (they commented that I looked good!), and worked a full day. It’s now 7:00 p.m. and I’m still going strong. On top of that, joint pain and swelling is much diminished. My wedding band easily slipped off my finger. That pesky right knee with the beat up cartilage was quiet. This was truly a day for rejoicing.

The Cimzia literature indicates 1-2 weeks before symptoms may improve. The pattern of the last two days is a good sign. But taking life one day at a time is a lesson that RA quickly teaches. Waxing my snow skis will wait until later this winter (now there’s hope!).

A CimPay card arrived in the mail yesterday. This nifty card, easily obtained by completing an online form, provides $500 of benefits for 12 months. That will come in handy to cover that $40 a month co-pay required by my insurance company. These cost savings can be used for shaving gear to get rid of those “mouse whiskers”!

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